Herombopag Olamine

Autologous hematopoietic stem cell (ASC) transplantation (ASCT) is an effective treatment method for patients with hematological disorders and malignant diseases. The patient's ASCs are harvested prior to radiotherapy/chemotherapy, cryopreserved and then transfused back after the high-dose radiotherapy/chemotherapy conditioning treatment. Since some patients develop thrombocytopenia after receiving ASCT, it is difficult for them to bear simultaneously the management of their original disease and thrombocytopenia. The present study aimed to evaluate the efficacy and safety of thrombocytopenia therapy with thrombopoietin receptor agonists (TPORAs) after ASCT.

We retrospectively analyzed the clinical safety and efficacy of TPORA treatment for the enrolled 20 patients who developed thrombocytopenia after ASCT. The measured parameters were prolonged isolated thrombocytopenia (PIT), secondary failure of platelet recovery (SFPR) and other calculated response index. Patients with platelet count (PC) ≤ 50×10⁹/L were treated with TPORA, namely with either eltrombopag (Elt), hetrombopag (Het), or avatrobopag (Ava).

The group of 20 patients, who received TPORA administration for their thrombocytopenia after ASCT, had a median age of 50 years (ranging between 17 and 60 years). The median administration time of TPORA application was 48 days (ranging from 7 to 451 days); an overall response rate (ORR) was 85% with no response in 15% of patients, while with complete response (CR) in 70% of patients and partial response (PR) in 15% of patients. The median platelet count was 19 × 10⁹/L before TPORA treatment and increased to 87×10⁹⁾/L after the treatment. The TPORA treatment was safe as only 4 patients (20%) displayed a mild transaminase elevation. No other reported side effects occurred, such as thrombosis, joint pain, diarrhea, and myelofibrosis. It was demonstrated that the short response time to TPORA treatment correlated to the fast platelet recovery, when the number of megakaryocytes in the bone marrow smear exceeded 35/4.5 cm² under a low magnification of 100 times (p = 0.015).

TPORA therapy for thrombocytopenia occurring after the radiotherapy/ chemotherapy-conditioned ASCT was well tolerated and effective for platelets recovery.

Avatrombopag, eltrombopag, and hetrombopag are three oral thrombopoietin receptor agonists used to treat thrombocytopenia. To investigate the pharmacokinetic properties, a fast and robust UPLC-MS/MS method was developed and validated for simultaneous determination of avatrombopag, eltrombopag, and hetrombopag in human plasma. Chromatographically separation was achieved on an Acquity BEH C₁₈ column using a gradient elution of methanol-water (20:80, v/v) and acetonitrile containing 0.1% formic acid at a flow rate of 0.4 mL/min within 4.5 min. The linearity was assessed over the range of 7.5-1500 ng/mL for avatrombopag, 50-10,000 ng/mL for eltrombopag, and 5-1000 ng/mL for hetrombopag. This method was validated with adequate results in terms of selectivity, precision (intra- and inter-day CV from 4.2% to 12.2%), accuracy (RE from -6.6% to 7.5%), dilution integrity, carryover, recovery, matrix effects, as well as stability of the analytes under various conditions. The developed approach has been successfully applied to the therapeutic drug monitoring of avatrombopag, eltrombopag, and hetrombopag in patients with immune thrombocytopenia.